A combined fluid dynamics, mass transport and cell growth model for a three-dimensional perfused biorector for tissue engineering of haematopoietic cells

Abstract

The three-dimensional (3D) architecture of bone marrow (BM) supports the renewal, maintenance, proliferation and differentiation of haematopoietic stem cells (HSCs). Efforts have been made towards the reconstruction of an ex vivo HSC culture system, which could have several potential clinical applications, especially in expansion of haematopoietic stem and progenitor cells for use in bone marrow transplantation (BMT). In the present study, a numerical model has been developed to investigate the fluid flow, shear stress, and nutrient distribution within a purpose-built scaffold placed inside a rotating wall perfused bioreactor (RWPB). Furthermore, a multi-lineage cellular growth model of haematopoietic cells is incorporated to mimic the complexity of the BM. The simulation results demonstrate that: (1) the fluid dynamics inside the scaffold are qualitatively similar to those in the in vivo BM microenvironment, and (2) the inlet conditions (inoculum density), transport properties (scaffold) and reaction parameters (consumption rates) are sufficient to support the growth of haematopoietic cells required for BMT applications. Specifically, the multi-lineage cellular growth model demonstrates that the system would be able to produce the minimum number of colony forming unit-granulocyte macrophage (CFU-GM) required for transplantation in an average patient. The numerical model presented here enables the optimisation of scaffold design parameters, fluid dynamics and mass transfer environment necessary for developing a suitable ex vivo haematopoietic system.